This proposal extends our scientific knowledge by developing more effective approaches to endovascular treatment of acute ischemic stroke (AIS) from large vessel occlusion (LVO). Removal of the clot, known as thrombectomy, is currently recommended for patients with acute stroke from LVO. Unfortunately, current thrombectomy approaches are successful in only 50-75% of patients with LVO causing disabling stroke sequelae. The objective of this study is to identify optimal thrombectomy techniques by studying how varying patient vessel anatomy affects the performance of clot removal devices. Our main hypothesis is that the efficacy of endovascular procedures can be improved by testing the performance of thrombectomy devices using patient-specific models of LVO. We will create complex, patient-specific 3-dimentional anatomical models from a database of AIS cases treated with thrombectomy. We will then use these models to test and compare success and failure rates of thrombectomy under different anatomical conditions simulating clinical situations commonly encountered in real-life neurointerventional practice. This study is significant because such knowledge can help clinicians perform endovascular stroke interventions and utilize suitable thrombectomy tools and approaches based on patient specific anatomical variants identified from pre-treatment imaging studies. Since successful thrombectomy is a major factor responsible for patient survival, recovery, and well-being after LVO-related AIS, this innovative project addresses the objective of the NINDS to accelerate the field of stroke research. In aim 1, we will create a library of patient-specific cerebrovascular occlusion models with variable anatomical characteristics. Variations in intracranial anatomy influence the performance of thrombectomy devices. When testing thrombectomy devices and techniques, it is critical to conduct such experiments under conditions that accurately recreate such variations particularly the ones that are likely to impede clot removal during thrombectomy. In aim#2, we will determine the effect of intracranial anatomy and clot morphology on the success of stent retriever thrombectomy utilizing the cerebrovascular occlusion model. Knowledge of different devices and techniques can improve the success rate of thrombectomy in clinical situations where endovascular treatment is more likely to fail complete removal of the clot (thrombus) will help the clinicians to more effectively treat AIS.